In conclusion, our findings demonstrate that the 8q24.13 amplification‐driven upregulation of TBC1D31 enhances its catalytic effect on Rab22A, thereby reducing the endolysosomal trafficking of EGFR for degradation, ultimately promoting the EGFR signaling and tumorigenesis in HCC cells (Figure 7l). Here, EGFR is linked to hepatocellular carcinoma.